Serious deep mycosis such as invasive candidiasis often becomes a fatal disease. Originally, it has been considered that a principal protective mechanism on the side of a host organism to fungi such as candida would be nonspecific immunization by neutrophils. When this protective mechanism normally functions, there is little risk of becoming infected with fungi. However, in recent years, a risk of suffering from deep mycosis has been boosted because of the increased number of patients with underlying diseases decreasing the immunological function of an organism, such as malignant tumors and AIDS, frequent use of anticancer agents or immunosuppressive agents, heavy use of antibacterial antibiotics or steroid hormone, long-term use of central venous hyperalimentation or venous catheterization, and the like (Non-Patent Document 1).
There are only 6 agents, i.e., amphotericin B, flucytosine, miconazole, fluconazole, itraconazole, and micafungin as agents for such deep mycosis. Amphotericin B has an extremely strong fungicidal action; however, it has a problem regarding side effects such as nephrotoxicity, and its clinical use is therefore limited. Flucytosine is rarely used alone at present because the agent has problems, e.g., development of resistance. Micafungin has a low activity against the genus Cryptococcus. The other agents are generically called an azole antifungal agent, and are most frequently used at present considering a balance between effectiveness and safety although their antifungal action tends to be generally inferior compared to that of amphotericin B (Non-Patent Document 2).
Currently, fluconazole-resistant Candida albicans (C. albicans) has been detected with a high frequency in oropharyngeal candidiasis lesions of AIDS patients to whom fluconazole has been repeatedly administered. What is more, most of the resistant strains show cross resistance to itraconazole and other azole agents. Further, such resistant strains have also been reported to be isolated from non-AIDS patients who developed chronic mucocutaneous candidiasis or deep candidiasis (Non-Patent Document 3). The problems regarding resistance seriously affect the management of patients with deep mycosis, the number of which has been steadily increasing (Non-Patent Document 3).
[Non-patent document 1]: Rinsho to Biseibutsu (Clinics and Microorganisms), Vol. 17: pp. 265-266, 1990
[Non-patent document 2]: Rinsho to Biseibutsu (Clinics and Microorganisms), Vol. 21: pp. 277-283, 1994
[Non-patent document 3]: Rinsho to Biseibutsu (Clinics and Microorganisms), Vol. 28: pp. 51-58, 2001